Drugs List

Therapeutic Indications

Uses

Ankylosing spondylitis requiring ulcer prophylaxis
Osteoarthritis requiring ulcer prophylaxis
Rheumatoid arthritis requiring ulcer prophylaxis

Contraindications

Children under 18 years
Asthma
Breastfeeding
Cerebrovascular haemorrhage
Gastrointestinal haemorrhage
Gastrointestinal perforation
Haematological disorder
Peptic ulcer
Renal impairment - creatinine clearance below 30 ml/minute
Severe cardiac failure
Severe hepatic impairment
Third trimester of pregnancy

Precautions and Warnings

Elderly
Females attempting to conceive
Risk factors for cardiovascular disorder
Acute porphyria
Cerebrovascular disorder
Coagulopathy
Congestive cardiac failure
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Hepatic impairment
Hepato-renal syndrome
History of gastrointestinal disorder
History of gastrointestinal perforation
History of gastrointestinal ulceration
Hypertension
Hypokalaemia
Hypomagnesaemia
Ischaemic heart disease
Long QT syndrome
Peripheral arterial circulatory disorder
Renal impairment
Second trimester of pregnancy
Systemic lupus erythematosus
Ulcerative colitis

May mask symptoms or signs of infections
NSAIDs may provoke or exacerbate asthma
Consider other first line treatment options in the elderly
Exclude malignancy, if alarm symptoms develop and gastric ulcer suspected
Contains hydroxybenzoate
Some formulations contain propylene glycol
Measure magnesium levels before and periodically during prolonged treatment
Discontinue if signs of gastro-intestinal bleeding occur
Ensure adequate vitamin D & calcium in patients at risk of osteoporosis
If visual disturbances occur, perform ophthalmic evaluation
May inhibit platelet aggregation - observe for signs of bleeding
Monitor for gastrointestinal toxicity
Monitor patients on long term therapy (over 1 year)
Monitor renal function in patients with cardiac impairment
Monitor renal function in patients with hepatic impairment
Advise patient to report unexplained nausea,vomiting,abdominal pain
Consider discontinuing if subacute cutaneous lupus erythematosus occurs
May prolong bleeding time
May reduce absorption of vitamin B12
Risk of gastro-intestinal bleeding increased in the elderly
Severe gastro-intestinal side effects may occur without warning
May affect results of some laboratory tests
Discontinue if severe abdominal symptoms develop
Discontinue treatment if skin rash or other allergic reaction occurs
Maintain treatment at the lowest effective dose
Advise patient not to take St John's wort concurrently
May cause impaired fertility
Advise patient to avoid sun exposure if subacute lupus erythematosus occurs

When a total daily dose of 1000 mg naproxen is not considered appropriate, alternative therapeutic regimens should be utilised.

This product contains very low levels of methyl- and propyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).

In the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with esomeprazole may alleviate symptoms and delay diagnosis.

Treatment with proton-pump inhibitors (PPIs) may lead to a slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter .

Prolonged use (greater than 1 year) of PPIs has been associated with hypomagnesaemia. Measure magnesium levels before and periodically during prolonged treatment. Patient should seek medical advice if symptoms of hypomagnesaemia occur (e.g. muscle twitches, tremors, vomiting, tiredness, loss of appetite) while taking proton pump inhibitors.

Low serum magnesium and/or low serum potassium may result in torsades de pointes (TdP) arrhythmia and should be used with caution in Long QT Syndrome.

Prolonged use (greater than 1 year) of PPIs has been associated with an increased risk of fracture. Ensure patients have an adequate intake of vitamin D and calcium.

Patients on long term treatment (particularly those treated for more than a year) should be kept under regular surveillance.

Esomeprazole may reduce the absorption of vitamin B12 due to hypo- or achlorhydria. This should be taken into consideration when treating patients with reduced body stores or risk factors of reduced vitamin B12 absorption on long-term therapy.

Use with caution in patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAIDs.

Renal function should be assessed before and during therapy. The final pathway for elimination of naproxen metabolites is largely by urinary excretion via glomerular filtration, use with great caution in patients with impaired renal function. Monitor serum creatinine or creatinine clearance before and during therapy. A twice daily dose of 500 mg naproxen may not be appropriate and may result in the accumulation of naproxen metabolites. Continue to monitor serum creatinine or creatinine clearance levels on a regular basis in patients with the following conditions:

The use of NSAIDs may be associated with acute renal failure in patients with severe hepato-cirrhosis. Treatment for concomitant coagulopathy could further increase the risk of severe bleeding in these patients.

Very infrequent cases of subacute cutaneous lupus erythematosus (SCLE) have been reported in patients taking PPIs. Drug-induced SCLE can occur weeks, months or even years after exposure to the drug. The MHRA have issued the following advice if a patient treated with a PPI develops lesions - especially in sun-exposed areas of the skin - and it is accompanied by arthralgia:

- advise them to avoid exposing the skin to sunlight
- consider SCLE as a possible diagnosis
- consider stopping use of the PPI unless it is imperative for a serious acid-related condition; a patient who develops SCLE with a particular PPI may be at risk of the same reaction with another
- in most cases, symptoms resolve on PPI withdrawal; topical or systemic steroids might be necessary for treatment of SCLE only if there are no signs of remission after a few weeks or months.

Pregnancy and Lactation

Pregnancy

The manufacturer contraindicates use during the third trimester of pregnancy. It should not be given to women attempting to conceive or during the first or second trimesters of pregnancy unless clearly necessary. The duration of treatment should be kept as short as possible.

Naproxen
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:
-Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension),
-Renal dysfunction, which may progress to renal failure with oligohydramnios.
The mother and the neonate, at the end of pregnancy, may be exposed to:
-Possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses,
-Inhibition of uterine contractions resulting in delayed or prolonged labour.

If treatment during the third trimester is unavoidable, foetal circulation should be monitored with Doppler sonography and therapy discontinued at the first signs of ductal constriction.
Naproxen should not be used during the first and second trimesters unless potential benefit outweighs the potential risk to the foetus. If short term use of an NSAID is required then ibuprofen at the recommended therapeutic doses would be the preferred choice. If an NSAID has been taken in early pregnancy Schaefer (2007) concludes that this does not require a termination of pregnancy or additional invasive diagnostic procedures.

Esomeprazole
Animal studies with esomeprazole do not indicate direct harmful effects with respect to embryonal/foetal development. Animal studies with racemic mixture do not indicate direct or indirect harmful effects with respect to pregnancy, parturition or postnatal development.

No clinical data on exposed pregnancies with the use of esomeprazole are available. As such, if a PPI is indicated, omeprazole should be used as a first choice. Inadvertent exposure in pregnancy, however, does not appear to represent a clinically significant risk to the embryo or foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Naproxen and esomeprazole is contraindicated in breastfeeding.

Naproxen
Although only excreted in breast milk in small quantities, naproxen has a long half life and there has been a reported serious adverse reaction in a breastfed neonate (a single case of prolonged bleeding time, haemorrhage and acute anaemia in a neonate whose mother was taking naproxen). Therefore other agents may be the preferred choice for breastfeeding women.
If an NSAID is considered essential ibuprofen is considered the drug of choice. Levels of ibuprofen in breast milk are negligible.

Esomeprazole
It is not known whether esomeprazole is excreted in human breast milk but the molecular weight is low enough that excretion into breast milk should be expected (Briggs). No studies in lactating women have been performed. Therefore esomeprazole should not be used during breast-feeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function tests
Agranulocytosis
Alopecia
Anaphylactic reaction
Angioedema
Anxiety
Arrhythmias
Arterial thrombosis
Arthralgia
Asthenia
Asthma
Blurred vision
Bronchospasm
Coma
Confusion
Conjunctivitis
Constipation
Convulsions
Depression
Dermatitis
Diarrhoea
Disturbances of appetite
Diverticulitis
Dizziness
Dream abnormalities
Dry mouth
Dyspepsia
Dyspnoea
Ecchymosis
Eosinophilia
Eructation
Erythema multiforme
Exacerbation of Crohn's disease
Fatigue
Flatulence
Fluid retention
Gastritis
Gastro-intestinal ulceration
Gastrointestinal bleeding
Glossitis
Gynaecomastia
Haematemesis
Headache
Hearing disturbances
Hyperhidrosis
Hyperkalaemia
Hypersensitivity reactions
Hypertension
Hyperuricaemia
Hypomagnesaemia
Increased risk of fractures
Infections
Insomnia
Interstitial nephritis
Leucopenia
Menstrual disturbances
Myalgia
Myocardial infarction
Nausea
Oedema
Oesophagitis
Palpitations
Paraesthesia
Proteinuria
Pruritus
Pyrexia
Rash
Rectal bleeding
Renal failure
Serum creatinine increased
Somnolence
Stevens-Johnson syndrome
Stomatitis
Subacute cutaneous lupus erythematosus
Sweating
Syncope
Tachycardia
Taste disturbances
Thirst
Tinnitus
Toxic epidermal necrolysis
Tremor
Ulcerative colitis
Urticaria
Vertigo
Vomiting
Weight changes

Presentation

Modified-release formulation of naproxen and esomeprazole

Drugs List

Therapeutic Indications

Uses

Ankylosing spondylitis requiring ulcer prophylaxis
Osteoarthritis requiring ulcer prophylaxis
Rheumatoid arthritis requiring ulcer prophylaxis

Dosage

Adults

Elderly

Patients with Renal Impairment

Patients with Hepatic Impairment

Additional Dosage Information

Contraindications

Children under 18 years
Asthma
Breastfeeding
Cerebrovascular haemorrhage
Gastrointestinal haemorrhage
Gastrointestinal perforation
Haematological disorder
Peptic ulcer
Renal impairment - creatinine clearance below 30 ml/minute
Severe cardiac failure
Severe hepatic impairment
Third trimester of pregnancy

Precautions and Warnings

Elderly
Females attempting to conceive
Risk factors for cardiovascular disorder
Acute porphyria
Cerebrovascular disorder
Coagulopathy
Congestive cardiac failure
Connective tissue disorder
Crohn's disease
First trimester of pregnancy
Hepatic impairment
Hepato-renal syndrome
History of gastrointestinal disorder
History of gastrointestinal perforation
History of gastrointestinal ulceration
Hypertension
Hypokalaemia
Hypomagnesaemia
Ischaemic heart disease
Long QT syndrome
Peripheral arterial circulatory disorder
Renal impairment
Second trimester of pregnancy
Systemic lupus erythematosus
Ulcerative colitis

May mask symptoms or signs of infections
NSAIDs may provoke or exacerbate asthma
Consider other first line treatment options in the elderly
Exclude malignancy, if alarm symptoms develop and gastric ulcer suspected
Contains hydroxybenzoate
Some formulations contain propylene glycol
Measure magnesium levels before and periodically during prolonged treatment
Discontinue if signs of gastro-intestinal bleeding occur
Ensure adequate vitamin D & calcium in patients at risk of osteoporosis
If visual disturbances occur, perform ophthalmic evaluation
May inhibit platelet aggregation - observe for signs of bleeding
Monitor for gastrointestinal toxicity
Monitor patients on long term therapy (over 1 year)
Monitor renal function in patients with cardiac impairment
Monitor renal function in patients with hepatic impairment
Advise patient to report unexplained nausea,vomiting,abdominal pain
Consider discontinuing if subacute cutaneous lupus erythematosus occurs
May prolong bleeding time
May reduce absorption of vitamin B12
Risk of gastro-intestinal bleeding increased in the elderly
Severe gastro-intestinal side effects may occur without warning
May affect results of some laboratory tests
Discontinue if severe abdominal symptoms develop
Discontinue treatment if skin rash or other allergic reaction occurs
Maintain treatment at the lowest effective dose
Advise patient not to take St John's wort concurrently
May cause impaired fertility
Advise patient to avoid sun exposure if subacute lupus erythematosus occurs

When a total daily dose of 1000 mg naproxen is not considered appropriate, alternative therapeutic regimens should be utilised.

This product contains very low levels of methyl- and propyl parahydroxybenzoate, which may cause allergic reactions (possibly delayed).

In the presence of any alarm symptom (e.g. significant unintentional weight loss, recurrent vomiting, dysphagia, haematemesis or melaena) and when gastric ulcer is suspected or present, malignancy should be excluded, as treatment with esomeprazole may alleviate symptoms and delay diagnosis.

Treatment with proton-pump inhibitors (PPIs) may lead to a slightly increased risk of gastrointestinal infections such as Salmonella and Campylobacter .

Prolonged use (greater than 1 year) of PPIs has been associated with hypomagnesaemia. Measure magnesium levels before and periodically during prolonged treatment. Patient should seek medical advice if symptoms of hypomagnesaemia occur (e.g. muscle twitches, tremors, vomiting, tiredness, loss of appetite) while taking proton pump inhibitors.

Low serum magnesium and/or low serum potassium may result in torsades de pointes (TdP) arrhythmia and should be used with caution in Long QT Syndrome.

Prolonged use (greater than 1 year) of PPIs has been associated with an increased risk of fracture. Ensure patients have an adequate intake of vitamin D and calcium.

Patients on long term treatment (particularly those treated for more than a year) should be kept under regular surveillance.

Esomeprazole may reduce the absorption of vitamin B12 due to hypo- or achlorhydria. This should be taken into consideration when treating patients with reduced body stores or risk factors of reduced vitamin B12 absorption on long-term therapy.

Use with caution in patients with a history of hypertension and/or mild to moderate congestive heart failure as fluid retention and oedema have been reported in association with NSAIDs.

Renal function should be assessed before and during therapy. The final pathway for elimination of naproxen metabolites is largely by urinary excretion via glomerular filtration, use with great caution in patients with impaired renal function. Monitor serum creatinine or creatinine clearance before and during therapy. A twice daily dose of 500 mg naproxen may not be appropriate and may result in the accumulation of naproxen metabolites. Continue to monitor serum creatinine or creatinine clearance levels on a regular basis in patients with the following conditions:

The use of NSAIDs may be associated with acute renal failure in patients with severe hepato-cirrhosis. Treatment for concomitant coagulopathy could further increase the risk of severe bleeding in these patients.

Very infrequent cases of subacute cutaneous lupus erythematosus (SCLE) have been reported in patients taking PPIs. Drug-induced SCLE can occur weeks, months or even years after exposure to the drug. The MHRA have issued the following advice if a patient treated with a PPI develops lesions - especially in sun-exposed areas of the skin - and it is accompanied by arthralgia:

- advise them to avoid exposing the skin to sunlight
- consider SCLE as a possible diagnosis
- consider stopping use of the PPI unless it is imperative for a serious acid-related condition; a patient who develops SCLE with a particular PPI may be at risk of the same reaction with another
- in most cases, symptoms resolve on PPI withdrawal; topical or systemic steroids might be necessary for treatment of SCLE only if there are no signs of remission after a few weeks or months.

Pregnancy and Lactation

Pregnancy

The manufacturer contraindicates use during the third trimester of pregnancy. It should not be given to women attempting to conceive or during the first or second trimesters of pregnancy unless clearly necessary. The duration of treatment should be kept as short as possible.

Naproxen
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:
-Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension),
-Renal dysfunction, which may progress to renal failure with oligohydramnios.
The mother and the neonate, at the end of pregnancy, may be exposed to:
-Possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses,
-Inhibition of uterine contractions resulting in delayed or prolonged labour.

If treatment during the third trimester is unavoidable, foetal circulation should be monitored with Doppler sonography and therapy discontinued at the first signs of ductal constriction.
Naproxen should not be used during the first and second trimesters unless potential benefit outweighs the potential risk to the foetus. If short term use of an NSAID is required then ibuprofen at the recommended therapeutic doses would be the preferred choice. If an NSAID has been taken in early pregnancy Schaefer (2007) concludes that this does not require a termination of pregnancy or additional invasive diagnostic procedures.

Esomeprazole
Animal studies with esomeprazole do not indicate direct harmful effects with respect to embryonal/foetal development. Animal studies with racemic mixture do not indicate direct or indirect harmful effects with respect to pregnancy, parturition or postnatal development.

No clinical data on exposed pregnancies with the use of esomeprazole are available. As such, if a PPI is indicated, omeprazole should be used as a first choice. Inadvertent exposure in pregnancy, however, does not appear to represent a clinically significant risk to the embryo or foetus.

The use of all medication in pregnancy should be avoided whenever possible; particularly in the first trimester. Non-drug treatments should also be considered. When essential, a medication with the best safety record over time should be chosen, employing the lowest effective dose for the shortest possible time. Polypharmacy should be avoided. Teratogens taken in the pre-embryonic period, often quoted as lasting until 14 to 17 days post-conception, are believed to have an all-or-nothing effect. Where drugs have a short half-life, and when the date of conception is certain, this may allow women to be reassured where drug exposure has occurred within this time frame. Further advice may be available from the UK National Teratology Information Service (NTIS) and through ToxBase, available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Lactation

Naproxen and esomeprazole is contraindicated in breastfeeding.

Naproxen
Although only excreted in breast milk in small quantities, naproxen has a long half life and there has been a reported serious adverse reaction in a breastfed neonate (a single case of prolonged bleeding time, haemorrhage and acute anaemia in a neonate whose mother was taking naproxen). Therefore other agents may be the preferred choice for breastfeeding women.
If an NSAID is considered essential ibuprofen is considered the drug of choice. Levels of ibuprofen in breast milk are negligible.

Esomeprazole
It is not known whether esomeprazole is excreted in human breast milk but the molecular weight is low enough that excretion into breast milk should be expected (Briggs). No studies in lactating women have been performed. Therefore esomeprazole should not be used during breast-feeding.

Neonates, infants born prematurely, those with low birth weight, those with an unstable gastrointestinal function or who have serious illnesses may require special consideration. For any infant, if a drug is prescribed to the nursing mother, it should be at the lowest practical dose and for the shortest time. When drug administration is unavoidable and breastfeeding is to continue, minimisation of exposure of the infant to the drug may sometimes be achieved by timing the maternal doses to just after a feeding episode. Infants exposed to drugs via breast milk should be monitored for unusual signs or symptoms. Interactions between the drug received by the infant from the mother's milk and medication prescribed for the infant should also be considered, for example, when the drug given to the infant may prevent metabolism of the drug received via breast milk.
Specialist advice is available from the UK Drugs in Lactation Advisory Service at https://www.midlandsmedicines.nhs.uk/content.asp?section=6&subsection=17&pageIdx=1

Side Effects

Abdominal pain
Abnormal liver function tests
Agranulocytosis
Alopecia
Anaphylactic reaction
Angioedema
Anxiety
Arrhythmias
Arterial thrombosis
Arthralgia
Asthenia
Asthma
Blurred vision
Bronchospasm
Coma
Confusion
Conjunctivitis
Constipation
Convulsions
Depression
Dermatitis
Diarrhoea
Disturbances of appetite
Diverticulitis
Dizziness
Dream abnormalities
Dry mouth
Dyspepsia
Dyspnoea
Ecchymosis
Eosinophilia
Eructation
Erythema multiforme
Exacerbation of Crohn's disease
Fatigue
Flatulence
Fluid retention
Gastritis
Gastro-intestinal ulceration
Gastrointestinal bleeding
Glossitis
Gynaecomastia
Haematemesis
Headache
Hearing disturbances
Hyperhidrosis
Hyperkalaemia
Hypersensitivity reactions
Hypertension
Hyperuricaemia
Hypomagnesaemia
Increased risk of fractures
Infections
Insomnia
Interstitial nephritis
Leucopenia
Menstrual disturbances
Myalgia
Myocardial infarction
Nausea
Oedema
Oesophagitis
Palpitations
Paraesthesia
Proteinuria
Pruritus
Pyrexia
Rash
Rectal bleeding
Renal failure
Serum creatinine increased
Somnolence
Stevens-Johnson syndrome
Stomatitis
Subacute cutaneous lupus erythematosus
Sweating
Syncope
Tachycardia
Taste disturbances
Thirst
Tinnitus
Toxic epidermal necrolysis
Tremor
Ulcerative colitis
Urticaria
Vertigo
Vomiting
Weight changes

Effects on Laboratory Tests

It is recommended to temporarily discontinue naproxen 72 hours before Porter-Silber adrenal function test.

Naproxen may interfere with some urinary assays of 5-hydroxy indoleacetic acid (5HIAA).

Esomeprazole may increase Chromogranin A (CgA) levels and may interfere with investigations for neuroendocrine tumours. To avoid this stop treatment temporarily for at least five days before CgA measurements are taken.

Overdosage

It is strongly recommended that the UK National Poisons Information Service be consulted on cases of suspected or actual overdose where there is doubt over the degree of risk or about appropriate management.

The following number will direct the caller to the relevant local centre (0844) 892 0111

Information may be obtained if you have access to ToxBase the primary clinical toxicology database of the National Poisons Information Service. This is available via password on the internet ( www.toxbase.org ) or if this is unavailable at the backup site ( www.toxbasebackup.org ).

Further Information

Last Full Review Date: October 2013

Reference Sources

British National Formulary, 66th Edition (September 2013-March 2014) Pharmaceutical Press, London.

CredibleMeds
Available at: https://www.crediblemeds.org/
Last accessed: 21 October, 2014

Drugs During Pregnancy and Lactation: Treatment Options and Risk Assessment, 2nd edition (2007) ed. Schaefer, C., Peters, P. and Miller, R. Elsevier, London.

Drugs in Pregnancy and Lactation: A Reference Guide to Fetal and Neonatal Risk, 9th edition (2011) ed. Briggs, G., Freeman, R. and Yaffe, S. Lippincott Williams & Wilkins, Philadelphia.

Summary of Product Characteristics: Vimovo 500 mg/20 mg modified-release tablets. AstraZeneca UK Limited. Revised October 2015.

MHRA Drug Safety Update April 2012. Proton pump inhibitors in long-term use: increased risk of fracture.
Available at: https://www.mhra.gov.uk
Last accessed: 20 September 2015

MHRA Drug Safety Update September 2015. Proton pump inhibitors: very low risk of subacute cutaneous lupus erythematosus.
Available at: https://www.mhra.gov.uk
Last accessed: 20 September 2015

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Naproxen Last revised: September 7, 2013
Last accessed: October 4, 2013

US National Library of Medicine. Toxicology Data Network. Drugs and Lactation Database (LactMed).
Available at: https://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT
Naproxen Last revised: September 7, 2013
Last accessed: October 4, 2013